Collision cross section (CCS) as a complementary parameter to characterize human and veterinary drugs

Area of Science:

• Analytical Chemistry
• Pharmacology

Background:

• Ion mobility spectrometry (IMS) coupled with mass spectrometry (MS) offers valuable collision cross-section (CCS) data for drug identification beyond mass-to-charge ratio (m/z).
• Limited availability of CCS data for drugs has hindered its widespread application as an identification parameter.

Purpose of the Study:

• To develop a robust CCS database for 92 human and veterinary drugs to facilitate their identification.
• To assess the inter-laboratory reproducibility of CCS measurements for selected compounds.
• To characterize the CCS of fragment ions for a more comprehensive analytical approach.

Main Methods:

• Traveling wave ion mobility spectrometry (TWIMS) was employed under positive ionization conditions with nitrogen as the drift gas.
• A database of 173 ions, including protonated ([M+H]+) and sodium adduct ([M+Na]+) species, was generated for 92 drugs.
• Fragmentation patterns and the CCS of resulting fragment ions were analyzed for 238 ions.

Main Results:

• A new CCS database for 92 drugs, with 37 compounds characterized for the first time, was established.
• High correlations between m/z and CCS were observed for both [M+H]+ (R² = 0.9518) and [M+Na]+ (R² = 0.9135) ions.
• The study demonstrated the matrix effect independence of CCS measurements in bovine urine samples, validating its use in biological matrices.

Conclusions:

• The proposed CCS database significantly expands the available data for human and veterinary drug identification.
• CCS is confirmed as a reproducible and reliable parameter for drug identification, even in complex biological matrices.
• The characterization of fragment ion CCS further enhances the specificity and confidence in drug identification using IMS-MS.